Lupus pleuritis: a relevant risk factor for pulmonary tuberculosis

The objective of the study was to evaluate risk factors for pulmonary tuberculosis in systemic lupus erythematosus (SLE). Clinical/laboratorial features of 1283 SLE patients (ACR criteria) followed at the Lupus Clinic were obtained from the electronic register database from 2001 to 2009. Pulmonary tuberculosis was diagnosed in 20 patients (1.6%) (TB+ group). As control group (TB-), 40 patients without tuberculosis matched for age, gender, ethnicity, age at SLE diagnosis, and disease duration were arbitrarily selected. All 20 patients of the TB+ group presented confirmed pulmonary tuberculosis from 1 to 23 years after SLE diagnosis (7.6 +/- 8.1 years). Frequencies of previous SLE involvements (cutaneous, articular, hematological, renal, pericarditis, pneumonitis, and central nervous system) were alike in TB+ and TB- groups (p > 0.05). In contrast, prior pleuritis was more frequent in the TB+ group (40% vs. 5%, p=0.001). In fact, pulmonary tuberculosis was diagnosed in 8/10 patients with previous pleuritis. Immunosuppressive and corticosteroid therapies at the moment of tuberculosis diagnosis were also similar in both groups (p > 0.05). We have identified pleuritis as a relevant risk factor for pulmonary tuberculosis, suggesting that previous pleural injury is a critical part of the complex interplay between altered immune system, socio-economic conditions, and increased susceptibility to this mycobacterial infection. Lupus (2010) 19, 1585-1590.

The time course of vasoconstriction and endothelin receptor A expression in pulmonary arterioles of mice continuously exposed to ambient urban levels of air pollution

The present study aimed to verify the time course of the effects of environmental levels of urban air pollution toxicity on lung arterioles. BALB/c mice (n = 56) were continuously exposed to selective chambers equipped with (filtered, F) or without (non-filtered, NF) filter devices for particles and toxic gases for 24 h/day, over 14, 21, 30 or 45 days. After exposure, we evaluated the lumen-wall relationship (an estimator of arteriolar narrowing), endothelial nitric oxide synthase (eNOS) and endothelin type A receptor (ETAr) expression in the vascular wall and inflammatory influx of the peribronchiolar area. Concentrations of fine particulate matter (PM <= 2.5 mu g/m(3)), nitrogen dioxide (NO(2)), black smoke (BS), humidity and temperature in both the environment and inside the chambers were measured daily. Filters cleared 100% of BS and 97% of PM inside the F chamber. The arteriole wall of the lungs of mice from NF chamber had an increased ETAr expression (p <= 0.042) concomitant to a decrease in the lumen/wall ratio (p = 0.02) on the early days of exposure, compared to controls. They also presented a progressive increment of inflammatory influx in the peribronchiolar area during the study (p = 0.04) and decrement of the eNOS expression on the 45th day of exposure in both vascular layers (p <= 0.03). We found that after 14 days of exposure, the ambient levels of air pollutants in Sao Paulo induced vasoconstriction that was associated with an increase in ETAr expression. These vascular results do not appear to be coupled to the progressive inflammatory influx in lung tissue, suggesting a down-regulation of vasoconstrictive mechanisms through an imbalance in the cytokines network. It is likely that these responses are protective measures that decrease tissue damage brought about by continuous exposure to air pollutants. (C) 2010 Elsevier Inc. All rights reserved.

Breast cancer five-year survival in New South Wales women, 1972 to 1991

This study of breast cancer survival is based on analysis of five-year relative survival of 38 362 cases of invasive breast cancer in New South Wales (NSW) women, incident between 1972 and 1991, with follow-up to 1992, using data from the population-based NSW Central Cancer Registry. Survival was ascertained by matching the registry file of breast cancers against NSW death certificates from 1972 to 1992, mainly by automated probabilistic linkage. Absolute survival of cases was compared with expected survival of age- and period-matched NSW women. Proportional hazard regression analysis was used for examination of the effects on excess mortality of age, period of diagnosis and degree of spread at diagnosis. Relative survival at five years increased from 70 per cent in 1972-1976 to 77 per cent in 1987-1991. Survival improved during the 1970s and in the late 1980s. Regression analysis suggested that part of the improved survival in the late 1980s was due to lesser degree of spread at diagnosis, whereas the improved survival during the 1970s may have been due to treatment. Survival was better for those aged 40-49 years (RR = 0.86) and worse for those aged greater than or equal to 70 years (RR = 1.22) compared with the referent group (60-69 years). Excess mortality was much less for those with invasive localised disease than those with regional spread (RR = 3.1) or metastatic cancer (RR = 15.5) at diagnosis. For the most recent period (1987-1991), relative five-year survival was 90, 70 and 18 per cent, respectively, for the three degree-of-spread categories.

Breast cancer five-year survival, by New South Wales regions, 1980 to 1991

Breast cancer five-year relative survival was calculated for 16 urban and rural regions in New South Wales (NSW) for cases incident in 1980-1991. Survival analysis employed cancer registry data linked with the death register, and age- and period-matched regional mortality of NSW women, Proportional hazard regression analysis was used to compare excess mortality in breast cancer cases in each region. The effect of region was significant (P < 0.05) in the analysis, after age and the follow-up variable (and their intel action) were adjusted for, although no region was significantly different from the referent group (chosen because of average relative five-year survival). When degree of spread and its interactions were entered into che model, the effect of region became nonsignificant. A significant linear trend (P < 0.05) in the adjusted relative risk for excess mortality in breast cancer cases was noted when regions were divided into quartiles based on socioeconomic status, with higher relative risk in low-socioeconomic-status groups; this effect also disappeared with adjustment for degree of spread at diagnosis. There was no general effect of rurality versus capital city or other metropolitan centres. This study demonstrates a small effect of region of residence and implied socioeconomic status on breast cancer survival in NSW women, but this becomes nonsignificant when the data are adjusted for degree of spread at diagnosis, This suggests that earlier diagnosis would he of benefit in reducing minor inequalities in breast cancer survival in NSW women.

Platelet protease-activated receptor 1 and membrane expression of P-selectin in pulmonary arterial hypertension

Introduction: Pulmonary arterial hypertension (PAH) is frequently associated with thrombotic events, particularly involving the pulmonary microcirculation at sites of vascular injury. We therefore decided to analyse protease-activated receptor 1 (PAR1), a key element in the activation of human platelets by thrombin, in PAH patients in stable clinical condition. Methods: Using flow cytometry, we analyzed platelet PAR1 density, PAR1-mediated exposure of P-selectin and the formation of platelet-leukocyte aggregates in 30 PAH patients aged 11 to 78 years (median 50.5 years). The control group consisted of 25 healthy subjects with the same age range as patients. Results: In patients, total platelet PAR1 density and uncleaved PAR1 density correlated negatively with platelet count (r(2) = 0.33 and r(2) = 0.34 respectively, p < 0.0015). In patients with a low platelet count (<150 x 10(9) platelets/L), both densities were increased relative to controls (82% and 33% respectively, p < 0.05). Thrombin peptide-induced platelet exposure of P-selectin was directly related to total and uncleaved PAR1 density (respectively, r(2) = 0.33 and r(2) = 0.29, p < 0.0025) and increased in subjects with low platelet count (46% versus those with normal platelet count, p < 0.05). Patients with low platelet count had decreased in vitro thrombin-induced formation of platelet-leukocyte aggregates (57% decrease versus controls, p < 0.05). Conclusions: There seems to be a subpopulation of PAH patients with increased propensity to thrombotic events as suggested by increased platelet PAR1 expression and PAR-mediated surface exposure of P-selectin associated with decreased platelet count. (C) 2009 Elsevier Ltd. All rights reserved.

The occurrence of cancer in a cohort of New South Wales coal miners

To describe the incidence of cancer in coal miners in New South Wales (NSW) between 1973 and 1992, an inception cohort of all male coal industry employees who entered the industry between 1 January 1973 and 31 December 1992 was constructed from the medical examination records of the Joint Coal Board. This cohort was matched with the NSW State Cancer Registry to determine the occurrence and type of cancer. In the cohort of 23 630 men, 297 developed 301 primary cancers in the 20-year period of observation. The standardised incidence ratio (SLR) for all cancers was 0.82. Stomach cancer has been reported to be common in coal miners but the SIR for stomach cancer was not higher than average in this cohort. A cluster of non-Hodgkin's lymphoma has been reported in a NSW coal mine but an increased risk of this cancer was not evident in the industry as a whole. Similarly a cluster of cases of brain tumour has been reported. In this cohort, the SIR for brain tumour was 1.05 (95 per cent confidence interval (CI) 0.57 to 1.76) and a risk for brain tumour remains unconfirmed. The SIR for malignant melanoma was 1.13 (CI 0.90 to 1.39) altogether and 2.02 (CI 1.31 to 2.98) for those workers who started in an open-cut mine. Overall, there does not appear to be a general risk of cancer in the NSW coal industry. Open-cut miners have an increased risk of malignant melanoma, which may be related to their exposure to the sun at work.

Long-Term Pulmonary Vascular Reactivity After Orthotopic Heart Transplantation by the Biatrial Versus the Bicaval Technique

Introduction. Advantages of the bicaval versus the biatrial technique have been reported, emphasizing atrial electrical stability and less tricuspid regurgitation. Objective. To analyze the impact of the surgical technique on long-term pulmonary pressures, contractility, and graft valvular behavior after heart transplantation. Methods. Among 400 orthotopic heart transplantation recipients from 1985 to 2010, we selected 30 consecutive patients who had survived beyond 3 years. The biatrial versus bicaval surgical technique groups included 15 patients each. Their preoperative clinical characteristics were similar. None of the patients displayed a pulmonary vascular resistance or pulmonary artery pressure over 6U Wood or 60 mm Hg, respectively. We evaluated invasive hemodynamic parameters during routine endomyocardial biopsies. Two-dimensional echocardiographic parameters were obtained from routine examinations. Results. There were no significant differences regarding right atrial pressure, systolic pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, cardiac index, systolic blood pressure, left ventricular ejection fraction, and mitral regurgitation (P > .05). Tricuspid regurgitation increased significantly over the 3 years of observation only among the biatrial group (P = .0212). In both groups, the right atrial pressure, pulmonary wedge capillary pressure, transpulmonary gradient, and pulmonary vascular resistance decreased significantly (P < .05) from the pre- to the postoperative examination. In both groups cardiac index and systemic blood pressure increased significantly after transplantation (P < .05). Comparative analysis of the groups only showed significant differences regarding right atrial pressure and degree of tricuspid regurgitation; the bicaval group showing the best performance. Conclusions. Both surgical techniques ensure adequate left ventricular function in the long term; however, the bicaval technique provided better trends in hemodynamic performance, as well as a lower incidence and severity of tricuspid valve dysfunction.

Comparison Between Perfadex and Locally Manufactured Low-Potassium Dextran Solution for Pulmonary Preservation in an Ex Vivo Isolated Lung Perfusion Model

Introduction. Lung tranplantation, a consolidated treatment for end-stage lung disease, utilizes preservation solutions, such as low potassium dextran (LPD), to mitigate ischemia reperfusion injury. We sought the local development of LPD solutions in an attempt to facilitate access and enhance usage. We also sought to evaluate the effectiveness of a locally manufactured LPD solution in a rat model of ex vivo lung perfusion. Methods. We randomized the following groups \?\adult of male Wistar rats (n = 25 each): Perfadex (LPD; Vitro life, Sweden); locally manufactured LPD-glucose (LPDnac) (Farmoterapica, Brazil), and normal saline solution (SAL) with 3 ischemic times (6, 12, and 24 hours). The harvested heart lung blocks were flushed with solution at 4 C. After storage, the blocks were connected to an IL-2 Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus) and reperfused with homologous blood for 60 minutes. Respiratory mechanics, pulmonary artery pressure, perfusate blood gas analysis, and lung weight were measured at 10-minute intervals. Comparisons between groups and among ischemic times were performed using analysis of variance with a 5% level of significance. Results. Lungs preserved for 24 hours were nonviable and therefore excluded from the analysis. Those preserved for 6 hours showed better ventilatory mechanics when compared with 12 hours. The oxygenation capacity was not different between lungs flushed with LPD or LPDnac, regardless of the ischemic time. SAL lungs showed higher PCO(2) values than the other solutions. Lung weight increased over time during perfusion; however, there were no significant differences among the tested solutions (LPD, P = .23; LPDnac, P = .41; SAL, P = .26). We concluded that the LPDnac solution results in gas exchange were comparable to the original LPD (Perfadex); however ventilatory mechanics and edema formation were better with LPD, particularly among lungs undergoing 6 hours of cold ischemia.

Survival in Patients With Idiopathic, Familial, and Anorexigen-Associated Pulmonary Arterial Hypertension in the Modern Management Era

Background-Novel therapies have recently become available for pulmonary arterial hypertension. We conducted a study to characterize mortality in a multicenter prospective cohort of patients diagnosed with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension in the modern management era. Methods and Results-Between October 2002 and October 2003, 354 consecutive adult patients with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension (56 incident and 298 prevalent cases) were prospectively enrolled. Patients were followed up for 3 years, and survival rates were analyzed. For incident cases, estimated survival (95% confidence intervals [CIs]) at 1, 2, and 3 years was 85.7% (95% CI, 76.5 to 94.9), 69.6% (95% CI, 57.6 to 81.6), and 54.9% (95% CI, 41.8 to 68.0), respectively. In a combined analysis population (incident patients and prevalent patients diagnosed within 3 years before study entry; n = 190), 1-, 2-, and 3-year survival estimates were 82.9% (95% CI, 72.4 to 95.0), 67.1% (95% CI, 57.1 to 78.8), and 58.2% (95% CI, 49.0 to 69.3), respectively. Individual survival analysis identified the following as significantly and positively associated with survival: female gender, New York Heart Association functional class I/II, greater 6-minute walk distance, lower right atrial pressure, and higher cardiac output. Multivariable analysis showed that being female, having a greater 6-minute walk distance, and exhibiting higher cardiac output were jointly significantly associated with improved survival. Conclusions-In the modern management era, idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension remains a progressive, fatal disease. Mortality is most closely associated with male gender, right ventricular hemodynamic function, and exercise limitation. (Circulation. 2010; 122: 156-163.)

Abnormal expression of telomerase/apoptosis limits type II alveolar epithelial cell replication in the early remodeling of usual interstitial pneumonia/idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a distinctive, usually fatal, type of chronic fibrosing interstitial pneumonia of unknown cause that increases in prevalence with advanced age, characterized by failure of alveolar re-epithelization and progressive scar formation. Recently, limitation of the replicative capacity of tissues determined by telomerase/apoptosis balance has been implicated in pathogenesis of age-related diseases. In this study, we validated the importance of the expression of type 2 alveolar epithelial cells telomerase protein and studied the relationships between telomerase and apoptosis in early remodeling of usual interstitial pneumonia. We determined type 2 alveolar epithelial cells density, telomerase expression, and apoptosis in surgical lung biopsies from 24 patients with usual interstitial pneumonia, and in normal lung tissues from 18 subjects. We used immunohistochemistry, deoxynucleotidyl transferase method of end labeling, electron microscopy, and histomorphometry to evaluate the amount of type 2 alveolar epithelial cells staining for surfactant-A, telomerase, and in situ detection of apoptotic cells. Unaffected areas of usual interstitial pneumonia and normal lung tissue had similar densities of type 2 alveolar epithelial cells, but a significant minor subpopulation of type 2 alveolar epithelial cells was telomerase positive and a large population was telomerase negative. A significant inverse association was found between low type 2, alveolar. epithelial cell telomerase expression and high apoptosis in unaffected areas of usual interstitial pneumonia. Although type 2 alveolar epithelial cell telomerase expression was higher than apoptosis in NLT group, no significant association was found between them. Electron microscopy confirmed epithelial apoptosis, alveolar collapse, and initial fibroplasia. We conclude that abnormal type 2 alveolar epithelial cells telomerase/apoptosis balance may reduce alveolar epithelial regenerative capacity, thus contributing to the early remodeling response in usual interstitial pneumonia. (C) 2010 Elsevier Inc. All rights reserved.

Tubal sterilisation, hysterectomy and decreased risk of ovarian cancer

We have examined the effect of tubal sterilisation and hysterectomy on risk of ovarian cancer in a large case-control study in eastern Australia involving 824 women aged 18-79 years, diagnosed with epithelial ovarian cancer between 1990 and 1993, and 855 controls randomly selected from the electoral roll. Relative risks for ovarian cancer were estimated using multiple categorical regression to adjust for age, parity, oral contraceptive use and other risk factors. Tubal sterilisation was associated with a 39% reduction in risk of ovarian cancer (RR 0.61, 95% Cl 0.46-0.85) and hysterectomy with a 36% reduction (RR 0.64, 95% Cl 0.48-0.85). Risk remained low 25 years after surgery and was reduced irrespective of sterilisation technique, and estimates were similar among various types of epithelial ovarian cancer. The greatest reduction (74%) was observed among women with primary peritoneal tumours. Pelvic infection and use of vaginal sprays or contraceptive foams were not related to ovarian cancer, while use of talc in the perineal region slightly but significantly increased risk among women with patent fallopian tubes. Reportedly heavy or painful menses, perhaps associated with retrograde flow, were associated with ovarian cancer, and reduction in risk of disease after hysterectomy was greatest among women who had heavy periods. Our findings support the theory that contaminants from the vagina, such as talc, and from the uterus, such as endometrium, gain access to the peritoneal cavity through patent fallopian tubes and may enhance the malignant transformation of ovarian surface epithelium. Surgical tubal occlusion may reduce the risk of ovarian cancer by preventing the access of such agents. (C) 1997 Wiley-Liss, Inc.

Fast-track rehabilitation for lung cancer lobectomy: a five-year experience

Objective: Fast-track rehabilitation is a group of simple measures that reduces morbidity, postoperative complication and accelerates postoperative rehabilitation reducing hospital stay. It can be applied to lung cancer lobectomy. Fast-track rehabilitation cornerstones are: minimally invasive surgical techniques using video-assisted and muscle sparring incisions, normovolemia, normothermia, good oxygenation, euglicemia, no unnecessary antibiotics, epidural patient-controlled analgesia, systemic opiods-free analgesia, early ambulation and oral feeding. Our objective is to describe a five-year experience with fast-track rehabilitation for lung cancer lobectomy. Patients and methods: A retrospective non-controlled study including 109 consecutive patients submitted to fast-track rehabilitation in the postoperative care of lung cancer lobectomy was performed. Only collaborative patients who could receive double-lumen intubation, epidural. catheters with patient-controlled analgesia, who had Karnofsky index of 100, previous normal feeding and ambulation, absence of morbid obesity, diabetes or asthma, were eligible. Postoperative oral feeding and aggressive ambulation started as soon as possible. Results: Immediate postoperative extubation even in the operation room was possible in 107 patients and oral feeding and ambulation were possible before the first hour in 101 patients. Six patients could not receive early oral feeding or ambulate due to hypnosis secondary to preoperative long effect benzodiazepines. Two patients could not ambulate immediately due to epidural catheter misplacement with important postoperative pain. Ninety-nine discharges occurred at the second postoperative day, four of them with a chest tube connected to a Heimlich valve due to air teak. No complication of early feeding and ambulation was observed. Postoperative hypnosis due to long duration benzodiazepines or pain does not allow early oral feeding or ambulation. Avoiding long duration preoperative benzodiazepines, immediate postoperative extubation, regional thoracic PCA and early oral feeding and ambulation were related to a lesser frequency of complication and a shorter hospital stay. Conclusion: Fast-track rehabilitation for lung cancer lobectomies can be safety performed in a selected group of patients if a motivated multidisciplinary group of professionals is available and seems to reduce postoperative complication and hospital stay. (C) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Updated Clinical Classification of Pulmonary Hypertension

The aim of a clinical classification of pulmonary hypertension (PH) is to group together different manifestations of disease sharing similarities in pathophysiologic mechanisms, clinical presentation, and therapeutic approaches. In 2003, during the 3rd World Symposium on Pulmonary Hypertension, the clinical classification of PH initially adopted in 1998 during the 2nd World Symposium was slightly modified. During the 4th World Symposium held in 2008, it was decided to maintain the general architecture and philosophy of the previous clinical classifications. The modifications adopted during this meeting principally concern Group 1, pulmonary arterial hypertension (PAH). This subgroup includes patients with PAH with a family history or patients with idiopathic PAH with germline mutations (e. g., bone morphogenetic protein receptor-2, activin receptor-like kinase type 1, and endoglin). In the new classification, schistosomiasis and chronic hemolytic anemia appear as separate entities in the subgroup of PAH associated with identified diseases. Finally, it was decided to place pulmonary venoocclusive disease and pulmonary capillary hemangiomatosis in a separate group, distinct from but very close to Group 1 (now called Group 1`). Thus, Group 1 of PAH is now more homogeneous. (J Am Coll Cardiol 2009;54:S43-54) (C) 2009 by the American College of Cardiology Foundation

Diagnosis, Assessment, and Treatment of Non-Pulmonary Arterial Hypertension Pulmonary Hypertension

The 4th World Symposium on Pulmonary Hypertension was the first international meeting to focus not only on pulmonary arterial hypertension (PAH) but also on the so-called non-PAH forms of pulmonary hypertension (PH). The term ""non-PAH PH"" summarizes those forms of PH that are found in groups 2 to 5 of the current classification of PH, that is, those forms associated with left heart disease, chronic lung disease, recurrent venous thromboembolism, and other diseases. Many of these forms of PH are much more common than PAH, but all of them have been less well studied, especially in terms of medical therapy. The working group on non-PAH PH focused mainly on 4 conditions: chronic obstructive lung disease, interstitial lung disease, chronic thromboembolic PH, and left heart disease. The medical literature regarding the role of PH in these diseases was reviewed, and recommendations regarding diagnosis and treatment of PH in these conditions are provided. Given the lack of robust clinical trials addressing PH in any of these conditions, it is important to conduct further studies to establish the role of medical therapy in non-PAH PH. (J Am Coll Cardiol 2009;54:S85-96) (C) 2009 by the American College of Cardiology Foundation